The development of new blood vessels, or angiogenesis, is essential for the growth and metastasis of most solid tumors. Targeting the endothelial cells that line tumor blood vessels is a promising anticancer strategy. We have recently identified several cell surface tumor endothelial markers (TEMs) that are conserved in both mouse and humans and that represent potentially useful targets for anticancer therapy. To determine whether these TEMs are in fact useful targets, we will begin translational studies using transplantable tumor models in mice. To target cell surface TEMs, we will develop antibodies recognize native TEM proteins on the cell surface of both mouse and human tumor vessels. We will begin our studies by attempting to target TEM8 and CD276, but later on may also attempt to target other cell surface TEMs such as TEM1, TEM5 or TEM7. Initial studies will involve labeling the antibodies with various markers that will allow us to monitor biodistribution following injection into tumor bearing mice. Subsequently, antibodies with the best sensitivity and specificity will be tested for their tumoricidal properties in preclinical mouse models and, if necessary, may be conjugated to small molecular weight drugs.